A unique coagulation enzyme has been isolated from malignant tissue, purified to homogeneity and partially characterized. This enzyme, cancer procoagulant, has been identified as a cysteine protease that initiates coagulation by directly activating factor X in the coagulation cascade. Studies of the enzymatic activity of cancer procoagulant in cell suspensions have demonstrated that it is present in the B16 mouse melanoma cells that were grown in defined medium (in the absence of fetal bovine serum) for 90 days, suggesting that the enzyme is not derived from serum components or extracellular substances but rather synthesized by the malignant cell. In addition, cell suspensions of the HT-29 human colon carcinoma cells and SV-40 transformed hamster fibroblasts contained the same procoagulant activity. In contrast normal hamster fibroblasts contained a procoagulant that was not DFP sensitive and appeared to be tissue factor. We are continuing to study the physical, chemical and enzymatic properties of this enzyme. In addition, we are studying the role of the enzyme in the malignant and metastatic process so as to understand whether the enzyme directly or indirectly facilitates the malignant process.